1,720,975 research outputs found
Lacosamide for the treatment of epilepsy
No full textIntroduction: Epilepsy is one of the most common neurological disorders. Despite the development of new antiepileptic drugs (AEDs), ∼ 30% of epilepsy patients experience recurrent seizures and even more experience side effects. Therefore, there is still need for new AEDs with enhanced effectiveness and tolerability. Areas covered: The article is based on a search using PubMed, including articles published between 1999 and 2013. It is focused on the pharmacokinetic, pharmacological and clinical data of lacosamide (LCM) for the treatment of epilepsy. Expert opinion: Along with favorable tolerability and pharmacokinetic profiles, LCM has been demonstrated to significantly reduce seizure frequency in patients with partial-onset seizures when prescribed as adjunctive treatment at doses of 200 and 400 mg/day. LCM has a unique mechanism of action, selectively enhancing slow inactivation of voltage-gated sodium channels. Its mechanism of action could be exploited to reduce the percentage of pharmacoresistant patients. Although LCM is not FDA approved for treatment of status epilepticus, it has demonstrated promising preliminary results. Large prospective studies are needed to verify these. In addition, the results of ongoing trials will help to confirm if LCM could be used as a monotherapy regimen in the treatment of partial-onset seizures and generalized tonic-clonic seizures
Investigational therapies for the treatment of narcolepsy
No full textNarcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep. While non-pharmacological treatments are sometimes helpful, more than 90% of narcoleptic patients require a pharmacological treatment. Areas covered: The present review is based on an extensive Internet and PubMed search from 1994 to 2017. It is focused on drugs currently in development for the treatment of narcolepsy. Expert opinion: Currently there is no cure for narcolepsy, with treatment focusing on symptoms control. However, these symptomatic treatments are often unsatisfactory. The research is leading to a better understanding of narcolepsy and its symptoms. New classes of compounds with possible applications in the development of novel stimulant/anticataplectic medications are described. H3 receptor antagonists represent a new therapeutic option for EDS in narcolepsy. JZP-110, with its distinct mechanism of action, would be a new therapeutic option for the treatment of EDS in the coming years. In the future, hypocretin-based therapies and immune-based therapies, could modify the clinical course of the disease. However, more information would be necessary to completely understand the autoimmune process and also how this process can be altered for therapeutic benefits
Pharmacokinetic drug evaluation of lacosamide for the treatment of partial-onset seizures
No full textThe goal of pharmacologic therapy with antiepileptic drugs (AEDs) is to reduce the frequency of seizures and achieve a seizure-free state with minimal side effects. However 30% of patients treated with available AEDs continue to experience uncontrolled seizures. There is still need for new AEDs with enhanced effectiveness and tolerability. Areas covered: The present manuscript is based on an extensive Internet and PubMed search from 1992 to 2017. It is focused on the pharmacokinetic properties of lacosamide (LCM) for the treatment of partial-onset seizures. Expert opinion: LCM is an anticonvulsant approved as add-on treatment or monotherapy of partial-onset seizures with or without secondary generalization. LCM shares many of the pharmacokinetic characteristics of an ideal AED. LCM displays linear and dose-proportional pharmacokinetics, rapid and complete absorption from the gastrointestinal tract, low plasma-protein binding, renal excretion and a terminal half-life that supports twice-daily dosing. Because the bioavailability and tolerability of oral and intravenous LCM are comparable, LCM offers the advantage of direct conversion from oral to intravenous administration, and vice versa, without the need for titration or dose adjustment. Further studies are needed to determine optimal timing, dosing, as well as the safety and efficacy of LCM in status epilepticus
Headache and endovascular procedures
No full textThe International Classification of Headache Disorders (ICHD-3 beta) includes headache attributed to intracranial endovascular procedures (EVPs). The aim of this review is to describe the clinical and pathophysiological aspects of headache related to vascular lesions and EVPs. Current studies regarding this issue are contradictory, although generally favouring headache improvement after EVPs. Further large studies are needed to adequately assess the effect of EVPs on headache
Pharmacokinetic and pharmacodynamic considerations for the clinical efficacy of perampanel in focal onset seizures
No full textIntroduction: Medical therapy is the mainstay of management of epilepsy. Despite the increasing
number of available antiepileptic drugs (AEDs), approximately one-third of epileptic patients do not
have adequate control of seizures. There is still a need for the development of new AEDs with enhanced
effectiveness and tolerability.
Areas covered: The present manuscript is based on an Internet and PubMed search (January 2005 to
August 2018). It is focused on pharmacokinetic and clinical data of perampanel (PER) for the treatment
of epilepsy.
Expert opinion: PER has a novel mechanism of action, which opens up new options for a rational
combination therapy. Phase III trials have demonstrated the efficacy and safety of PER as adjunctive
therapy for the treatment of partial-onset seizures (POS) and primary generalized tonic–clonic seizures
in patients aged ≥12 years. PER is also approved by FDA as monotherapy for the treatment of POS.
A clinical trial is ongoing to verify the efficacy and safety of PER monotherapy in untreated patients with
POS. In the future, head-to-head comparisons are needed to determine the exact position of PER
relative to other AEDs. Moreover, further studies are needed to evaluate the efficacy and safety of PER in
patients aged <12 years
Restless legs syndrome in internal medicine
No full textRestless legs syndrome/Willis-Ekbom Disease (RLS/WED) is a common but still underdiagnosed neurological disorder. RLS/WED might impair nocturnal rest causing decreased alertness, depression, reduced job performance and poor quality of life. RLS/WED can occur as an isolated disease, mostly at a young age, or can be associated with comorbidities such as cardiovascular disease, diabetes, renal failure, arterial hypertension and peripheral neuropathy. The literature also offers some evidence of an association with gastrointestinal, rheumatological, pneumological, and neoplastic disorders. It is important to be aware of these associations in order to promptly recognize RLS/WED and also to think about an underlying medical condition when a patient reports symptoms of RLS/WED
Investigational approaches to therapies for restless legs syndrome
No full textIntroduction: Restless Legs Syndrome (RLS) is a common neurological disorder that impairs nocturnal rest, causing decreased alertness, depressed mood, reduced job performance and poor quality of life. In patients affected by severe RLS, pharmacological treatment is mandatory. Areas covered: The present review is based on an extensive Internet and PubMed search from 1994-2014. It focuses on drugs currently in development for the treatment of RLS. Expert opinion: The drugs currently available for treating RLS do not always allow the patient to obtain a dose capable of controlling the symptoms, particularly in the long term. There is still the need for effective and well-tolerated new drugs. Monoamine oxidase B inhibitors could be good candidates for the initial treatment of RLS, sparing stronger dopaminergic agents for later stages of the disease. Oxycodone-naloxone has demonstrated a significant and sustained effect on patients with severe RLS inadequately controlled with first-line drugs; it could be used as a long-term treatment option in severe cases of RLS for which alternative satisfactory drug regimens are unavailable. There is a paucity of data comparing medications in head-to-head trials to determine their relative effectiveness and adverse event profiles. Furthermore, there is also a need for further studies that evaluate nondopaminergic agonists and combination therapies for treating RLS
ADMET considerations when prescribing novel therapeutics to treat restless legs syndrome
No full textIntroduction: Restless legs syndrome (RLS) is a commonly occurring sensory motor disorder that might impair nocturnal rest causing decreased alertness, depression, reduced job performance and poor quality of life. In patients affected by severe RLS, a pharmacological treatment is mandatory.Areas covered: The present review is based on a search using PubMed from 1994 to 2014. It is focused on the Absorption, Distribution, Metabolism, Elimination and Toxicology (ADMET) characteristics of drugs currently used and under development for the treatment of RLS.Expert opinion: The drugs currently available for RLS treatment do not always provide an optimal control of symptoms. There is still need for effective and well-tolerated new drugs. Long-acting dopamine agonists showed better efficacy than short-acting compounds in the treatment of severe RLS. There seems to be an inverse relationship between the half-life of the compound and the development of augmentation. Monoamine oxidase B inhibitors could be good candidates for initial treatment of RLS, sparing stronger dopaminergic agents for later stages of the disease. Oxycodone-naloxone demonstrated a significant and sustained treatment effect for patients with severe RLS insufficiently treated with first-line drugs and could be used as a long-term treatment in severe RLS when alternative satisfactory drug regimens are unavailable
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